Renal Disease and Pregnancy

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Renal Disease and Pregnancy

• Matt Hall
• Nottingham Renal Unit
• SpR Club Belfast

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• Sex
• Drugs
• Rock and roll

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Sex
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Pregnancy and CKD
?
National Statistics Online. Conception statistics
2008. http//www.statistics.gov.uk/downloads/theme
_health/conceptions2008/conceptions08.pdf Brown
JH, Maxwell AP, McGeown MG. Irish J Med.
2001 Barua M, Hladunewich M, Keunun J et al.
Clin J Am Soc Nephrol. 20083392/396
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Pregnancy and CKD
Approximate number of pregnancies per year in UK
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Maternal and fetal risks
Maternal risks Is pregnancy going to make my
kidney disease worse?
Fetal risks Will I take home a healthy baby?
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Maternal and fetal risks
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Factors associated with adverse outcomes
Baseline renal function?
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Baseline renal function?
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Baseline renal function?
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Baseline renal function?
p0.027
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Baseline renal function?


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Factors associated with adverse outcomes
Baseline renal function - yes
Baseline blood pressure?
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Blood pressure?
Neonatal death risk Neonatal death risk
Diastolic BP Absolute risk
lt70 0.9
70-80 3.2
80-90 3.6
gt90 or treated 15.3
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Blood pressure?
p0.08
p0.009
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Blood pressure?

• 43 pregnancies in 30 women with CKD (serum
  creatinine 110 to 490 µmol/l)
• Hypertension was present from conception in 26
  (60).
• Logistic regression identified uncontrolled
  hypertension at conception as an independent risk
  factor for fetal death
• RR fetal death with MAPgt 105mmHg at conception
  10.5
• Accelerated loss of maternal renal function in 7
  patients, all of whom had hypertension

• 168 pregnancies in 118 women with IgA
  nephropathy.
• Perinatal mortality 33 in women with BPgt140/90
  versus 1 with BPlt140/90
• (Hypertension not identified as a risk factor
  for progression of maternal disease.)

Jungers P et al. Pregnancy in women with impaired
renal function. Clin Nephrol 199747(5)218-288 Ab
e S. Pregnancy in IgA nephropathy. Kidney
International 1991401098-1102
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Factors associated with adverse outcomes
Proteinuria ?
Baseline renal function - yes
Baseline blood pressure - yes
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Proteinuria
Second trimester ACRgt3mg/mmol
X
Women without CKD
OR 1.9 preterm delivery
Second trimester ACRgt20mg/mmol
OR 4.7 preterm delivery
Diabetes and hypertension
Women with CKD Creat gt 124µmol /l
Proteinuria gt 3g/d
No impact on outcome
Proteinuria lt 3g/d
Pregnancy (n19)
Women with CKD
Proteinuria and pregnancy assoc with PALRF
No pregnancy (n31)
Franceschini N et al. Maternal urine albumin
excretion and pregnancy outcome. Am J Kindy Dis.
200545(6)1010-1018 Jones DC, Hayslett JP.
Outcome of pregnancy in women with moderate or
severe renal insufficiency. New Engl J Med
1991336(4)226-223 Hemmelder MH et al.
Proteinuria a risk factor for pregnancy-related
renal function decline in primary glomerular
disease? A,m J Kidney Dis 19952691)187-192
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Proteinuria?
Imbasciati E et al. AJKD 200749753
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Proteinuria?
PALRF PALRF
Yes No p value

n 6 21
Maternal age (years) Mean (SD) 33.0 (3.7) 30.4 (3,3) 0.103
Gravidity Median (range) 3 (1-4) 3 (1-5) 0.057
Underlying glomerular disease n () 2 (33) 13 (69) 0.357

Baseline serum creatinine (µmol/l) Mean (SD) 111 (46) 81 (20) 0.027
Baseline eGFR (ml/min) Mean (SD) 63 (28) 79 (16) 0.077
Baseline proteincreatinine ratio (mg/mmol creatinine) Median (IQR) 29 (206) 46 (272) 0.345
Rate of decline in eGFR prior to conception (ml/min/year) Median (IQR) 0.44 (4.15) -0.50 (3.52) 0.932

Baseline systolic BP (mmHg) Mean (SD) 143.1 (18.3) 136.6 (20.8) 0.08
Baseline diastolic BP (mmHg) Mean (SD) 81.0 (4.7) 71.6 (9.7) 0.009
Receiving antihypertensives n () 5 (83.3) 7 (33.3) 0.003
Table. Demographic and clinical parameters of study cohort Table. Demographic and clinical parameters of study cohort Table. Demographic and clinical parameters of study cohort Table. Demographic and clinical parameters of study cohort Table. Demographic and clinical parameters of study cohort
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Proteinuria
p0.60
p0.03
p0.86
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Factors associated with adverse outcomes
Proteinuria maternal? no fetal? yes
Baseline renal function - yes
Baseline blood pressure - yes
Aetiology of kidney disease?
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Aetiology of kidney disease?
Perinatal loss Preterm delivery Renal function decline Permanent blood pressure increase
FSGS (n85) 23 32 13 10
Membranous GN (n110) 4 35 3 3
IgA nephropathy (n268) 15 21 12 12
MC GN (n278) 12 9 2 7
Diabetic nephropathy (n97) 6 36 32 58
Polycystic disease (n464) 3 10 3 14
Reflux nephropathy (n137) 7 15 0.7 11
Comparison of pregnancy outcomes by aetiology of CKD. FSGS, focal segmental glomerulosclerosis GN, glomerulonephritis MC, mesangiocapillary. Comparison of pregnancy outcomes by aetiology of CKD. FSGS, focal segmental glomerulosclerosis GN, glomerulonephritis MC, mesangiocapillary. Comparison of pregnancy outcomes by aetiology of CKD. FSGS, focal segmental glomerulosclerosis GN, glomerulonephritis MC, mesangiocapillary. Comparison of pregnancy outcomes by aetiology of CKD. FSGS, focal segmental glomerulosclerosis GN, glomerulonephritis MC, mesangiocapillary. Comparison of pregnancy outcomes by aetiology of CKD. FSGS, focal segmental glomerulosclerosis GN, glomerulonephritis MC, mesangiocapillary.
No convincing evidence of effect of aetiology on
outcomes
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Aetiology of kidney disease?
SLE
Renal dysfunction
Antiphospholipid syndrome
Anti-Ro antibodies
Hypertension
Medication
All associated with adverse outcomes
Not the SLE label itself
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Aetiology of kidney disease?
Reflux nephropathy
Increased risk of UTI
Neonatal morbidity and mortality
Preterm labour
Maternal mortality
Increased risk of pyelonephritis
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Aetiology of kidney disease?
Diabetes
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Aetiology of renal disease?
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Factors associated with adverse outcomes
Baseline renal function - yes
Proteinuria maternal? no fetal? yes
Baseline blood pressure - yes
Aetiology of kidney disease not really
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Management of CKD and hypertension in pregnancy
Masterful inactivity
Hawk-like observation
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Management of CKD in pregnancy
Preconception counselling
Limited interventions
Pre-eclampsia prophylaxis
Medicines management
Blood pressure control
Thrombo- prophylaxis
Urinary tract infection treatment
Dialysis manipulation
Immunosuppressant tweakage
Timing of delivery
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Management of CKD and hypertension in
pregnancyPre-eclampsia prophylaxis
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Management of CKD and hypertension in
pregnancyPre-eclampsia prophylaxis
Aspirin 75mg od
Systematic review
37560 women
All women
High risk women
17 relative risk reduction
25 relative risk reduction
NNT 72
NNT 19
Perinatal death RRR 14
Preterm delivery RRR 8
SGA RRR 10
Duley L, Henderson-Smart DJ, Meher S, King JF.
Antiplatelet agents for preventing pre-eclampsia
and its complications. Cochrane Database
Syst.Rev. 2007 Apr 18(2)(2)CD004659.
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Management of CKD and hypertension in
pregnancyThrombo-prophylaxis

• Not evidence based
• Different practices between (and within) centres.

Nephrotic syndrome RR VTE 1.7
Pregnancy RR VTE 4.3
?
Heavy proteinuria RR VTE ?
Pregnancy RR VTE 4.3
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Management of CKD and hypertension in
pregnancyThrombo-prophylaxis
Add-up risk factors
Prophylactic LMWH
No treatment
If renal impairment, monitor Factor Xa levels
Low threshold for investigating suspected VTE
Treat until 6 weeks postpartum
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Management of CKD and hypertension in
pregnancyUrinary tract infection
Pyelonephritis
Asymptomatic bacteruria
4x increased risk in pregnancy
21 risk of progression if untreated
Treatment of asymptomatic bacteruria in pregnancy
reduces the incidence of pyelonephritis by 75
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Management of CKD and hypertension in
pregnancyUrinary tract infection
Antibiotic treatment of asymptomatic bacteruria
is indicated to reduce the risk of pyelonephritis
in pregnancy
Antibiotic treatment of asymptomatic bacteruria
was associated with a reduction in the incidence
of low birth weight babies (RR 0.66 (0.49-0.89))
Based on studies from 1960-1970s
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Management of CKD and hypertension in
pregnancyUrinary tract infection
n85,484
Pyelonephritis
Asymptomatic bacteruria
Non-pyelonephritic UTI
Preterm birth 8.3
Preterm birth 7.7
Preterm birth 7.2
Small for gestational age 18.9
Small for gestational age 16.5
Small for gestational age 16.1
After adjusting for confounding covariates, no
increased risk of preterm birth or small infant
in women exposed to urinary tract infection.
Chen YK et al. Acto Obstet Gynecol Scand
201089(7)882-888
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Management of CKD and hypertension in
pregnancyUrinary tract infection
In pregnancy
Asymptomatic bacteruria
Non-pyelonephritic UTI
Treat
Pyelonephritis
Second or more episode in pregnancy?
Asymptomatic bacteruria
Non-pyelonephritic UTI
Treat
Prophylaxis
Pyelonephritis
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Management of CKD and hypertension in
pregnancyBlood pressure control
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Management of CKD and hypertension in
pregnancyBlood pressure control
Do not treat to DBPlt80mmHg
Target BP lt150/100
Chronic hypertension
Target BP lt140/90
Chronic hypertension CKD
Target BP ? and treat with what?
Chronic hypertension proteinuric CKD
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Management of CKD and hypertension in
pregnancyBlood pressure control
Target BP lt140/90
Chronic hypertension proteinuric CKD
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Pregnancy and dialysis
?
National Statistics Online. Conception statistics
2008. http//www.statistics.gov.uk/downloads/theme
_health/conceptions2008/conceptions08.pdf Brown
JH, Maxwell AP, McGeown MG. Irish J Med.
2001 Barua M, Hladunewich M, Keunun J et al.
Clin J Am Soc Nephrol. 20083392/396
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Pregnancy and dialysis
An average sized renal unit in the UK would
expect to treat one pregnant patient on dialysis
every four years
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Pregnancy and dialysis
How do you diagnosis pregnancy in a woman on
dialysis?
Amenorrhoea?
Pregnancy test from Boots?
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Pregnancy and dialysis
How do you diagnosis pregnancy in a woman on
dialysis?
Intradialytic hypotension?
Serum ßhCG
Early ultrasound
Elevated Serum ßhCG but no fetal heart beat?
Serial ßhCG
Repeat ultrasound in 1-2 weeks
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Pregnancy and dialysis
Target weight Increase by 1.5kg over first trimester 0.2-0.4 kg/week from week 15 Weekly clinical evaluation
Blood pressure Target blood pressure lt140/90 Do not treat to DBPlt80mmHg
Anaemia ESA requirement increases by 85 at 28 weeks Target Hb 10-11g/dl
Nutrition Protein intake gt1.8g/kg/day Energy intake 30kcal/kg/day Water soluble vitamin and folic acid supplementation
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Pregnancy and dialysis
Befriend an obstetrician

• Fetal growth monitoring every 1 2 weeks
• Liquor volume monitoring every 1 -2 weeks
• CTG monitoring every dialysis session from 25
  weeks

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Pregnancy and dialysis
PD?
Yes!

• Conception rates may be lower
• Infection rates no higher
• No contraindication to Caesarean

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Pregnancy and dialysis
HD?
Yes!
How much?
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Pregnancy and dialysis
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Pregnancy and dialysis
plt0.05
Hou S. Hemodialysis International 20048167-171
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Pregnancy and dialysis
Hou S. Hemodialysis International 20048167-171
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Pregnancy and dialysis
Hou S. Hemodialysis International
20048167-171 Barua M et al. Clin J Am Soc
Nephrol 20083392-396
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Pregnancy and dialysis
Hou S. Hemodialysis International
20048167-171 Barua M et al. Clin J Am Soc
Nephrol 20083392-396
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Pregnancy and dialysis
Historic observations Nocturnal HD
Preterm delivery 90 50
IUGR/SGA 90 17
Pre-eclampsia 75 0
Perinatal death 50 17
Williams D, Davison J. BMJ 2008336211-215 Barua
M et al. Clin J Am Soc Nephrol 20083392-396
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Pregnancy and dialysis
How much?
As much dialysis as you can facilitate and
certainly gt20 hours/week
Maintain pre-dialysis urea lt 15mmol/l
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Transplant and pregnancy
Fertility returns within 1 -2 months of transplant
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Renal disease and pregnancy renal transplant
Pregnancy outcomes following transplant
are vastly better than if still on dialysis -
95 success

• General guidelines
• Wait 2 years post-transplant (some say 12-18
  months)
• Stable renal function
• Minimal proteinuria
• Minimal or well-controlled hypertension
• No transplant rejection
• Minimal levels of appropriate immunosuppression

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Renal disease and pregnancy renal transplant
Pregnancy outcomes are predicted by baseline
kidney function
Baseline creatinine Complicated pregnancy Successful outcome
lt125 µmol/l 30 97
gt125 µmol/l 82 75
Persistent post pregnancy kidney
function impairment develops in 15 of transplant
patients
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Renal disease and pregnancy renal transplant
children
Children born to mothers with a renal transplant
do well in general
Complications are due mainly to preterm delivery
and low birth weight
Overall, 16 of children have special educational
needs (cf. 11 in USA general population)
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Transplant dysfunction in pregnancy

• Same causes
• Same investigations (caution but not
  contraindication to radiation exposure)
• Different treatment

Infection
Rejection
Obstruction
Medication
Biopsy if indicated.
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Drugs
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Drugs, CKD and pregnancy

• Altered pharmacodynamics
• Potential teratogenicity

Check the BNF
Learn what you can use
Immunosuppressants
Antibiotics
Antihypertensives
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Drugs, CKD and pregnancy
Antihypertensives

1. ACE inhibitors
2. ARBs
3. Spironolactone
4. Aliskiren
5. Moxonidine
6. Minoxidil
7. Diltiazem

1. Labetalol
2. Methyldopa
3. Nifedipine
4. Hydralazine

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Drugs, CKD and pregnancy
Antibiotics

1. Quinolones
2. Tetracyclines

• Trimethoprim
• (not in 1st trimester)
• 2. Nitrofurantoin
• (not in 3rd trimester)

1. Cephalosporins
2. Penicillins
3. Gentamicin
4. Erythromycin

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Drugs, CKD and pregnancy
Immunosuppressants

1. Mycophenolate mofetil
2. Mycophenolic acid
3. Sirolimus
4. Methotrexate
5. Cyclophosphamide
6. ATG / OKT3

1. Prednisolone
2. Cyclosporine
3. Tacrolimus
4. Azathioprine

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